The long range objective of this project is to define the changes which occur in lens crystallins during the development of human senile cataract. Emphasis will be placed on studying high molecular weight (HMW) protein aggregates in the lens and determining the possible significance of such aggregates in cataractogenesis. We will investigate aggregate formation in experimental and human senile cataract and as a function of age in human lens. While the major emphasis will be on human senile and X-ray-induced cataract we would also have the opportunity to examine whether HMW proteins are formed in other types of experimental cataracts. The proposed investigations are concerned with determining the relative proportions of alpha, beta and gamma-crystallins present in the aggregates, the type of binding involved and possible mechanisms of aggregate formation. Special emphasis will be placed on the role of disulfide bonds in the formation of HMW aggregates during the development of experimental and human senile cataract. Because of the possible involvement of glutathione (GSH) in the maintenance of normal crystallins certain aspects of GSH metabolism such as the levels of free and protein-bound tripeptide and the activities of glutathione reductase, glucose-6-phosphate dehydrogenase, gamma-glutamyl transpeptidase and glutathione peroxidase will be investigated.